L1 cell adhesion molecules (L1CAMs) are transmembrane immunoglobulin-like proteins that play important roles in nervous system development. Genes encoding L1CAMs - L1, NrCAM, CHL1, and Neurofascin - have been highly associated with genetically complex neurological disorders including addiction, schizophrenia, autism, and Hirschsprung's disease. In addition, mutations in the L1 gene directly underlie the neurological X-linked L1 Syndrome. Interestingly, siblings with the same L1 allele can show highly variable penetrance and severity of symptoms, consistent with the presence of L1-interacting genes. C. elegans has a single gene,
sax-7, which encodes a canonical L1CAM with major hallmarks of mammalian L1CAMs. We have identified a novel interaction between
sax-7 and the Ras-mitogen activated protein kinase (MAPK) signaling pathway. The Ras GTPase, encoded by the
let-60 gene in C. elegans, has been identified to play key roles in development, cell signaling, and cancer. In C. elegans, LET-60 is key for proper development of several tissues, notably of the vulva. We discovered that loss of
sax-7 function enhances
let-60 gain-of-function (gf) multivulval phenotype. Loss of
sax-7 function also synergizes with
let-60 (gf), resulting in synthetic Clr phenotypes, hypo-osomotic sensitivity, and lethality. In addition to identifying novel roles for
sax-7, these findings also reveal a link between SAX-7 and intracellular signaling that likely have implications on disease manifestation. Here, we provide a more detailed study of these phenotypes and use the well-established vulva model to dissect the interplay between L1CAMs and Ras.